Why is mucormycosis more difficult to cure than more common mycoses?

Abstract

Although considered to be a rare infection, mucormycosis (zygomycosis) has emerged as the second most common invasive mould infection. Despite the advent of newer antifungal agents, mortality rate of mucormycosis remains exceedingly high. Successful management of mucormycosis requires early diagnosis, reversal of underlying predisposing risk factors, surgical debridement and prompt administration of active antifungal agents. However, mucormycosis is not always amenable to cure. There are challenging obstacles that lead to difficulties in management of amphotericin B. These include unique host-based risk factors for mucormycosis, the fungus' resistance to innate host defences and distinctive features of its immunopathogenesis, such as extensive angioinvasion, increased virulence and use of chelators by the fungus as siderophores. In addition to these obstacles, the difficulties in early diagnosis, including nonspecific clinical manifestations, lack of serological methods, as well limitations of culture and molecular methods, lead to delay in initiation of antifungal therapy. Finally, the variability of susceptibility to amphotericin B and resistance to most other conventional antifungal agents leads to major limitations in successful treatment of this devastating infection.

Update on Fungal Disease: From Establish Infection to Clinical Manifestation

“…The epidemiology of zygomycosis is still unclear because of the difficult diagnosis [161]. The mortality of zygomycosis is high and has been estimated at 50-100%, giving a higher mortality index than either systemic candidiasis or aspergillosis [160,[162][163][164].…”

Rhinocerebral Mucormycosis: Clinical Outcome, Diagnosis, Treatment – Review of the Literature

“…For comparison: the sinonasal -7.1% and sinonasaloorbital -6.1% forms were not often found. This disease may occur in all patients regardless of age and gender [9,12]. Often the most vulnerable age group were young adults with varying degrees of deficiency of the immune system and also those treated for other systemic diseases.…”

“…Diabetes mellitus, malignancies, severe injuries and transplantations were most frequently mentioned as predisposing factors in world literature. Uncontrolled diabetes and trauma dominate in developing countries, while in highly developed countries, diabetes and cancer seem to be most often related to any forms of fungal infection [12]. Roden's et al [13] research showed that the most frequently predisposing factor is diabetes, present in 36% cases, while others are 17% forms of various malignancies, while 95% of them are hematological tumors.…”

“…Histological findings may be atypical, especially if antifungal therapy was scheduled before collecting some samples or scrubs. Moreover, the lack of specific symptoms and biomarkers, and a high risk of damage to the material during collection and processing, are factors impeding definitive diagnosis [3,5,12,24]. In the case of rhinoorbital mucormycosis, any material for microscopic examination is taken mostly from nose secretions, the nasal cavity and a biopsy of the infected tissue [16] (Table 2).…”

Immune responses to Mucorales growth forms: Do we know everything?

“…Challenging host immune response is another possible reason that may play a role. 13 There are challenging obstacles that lead to difficulties in the management of invasive mucormycosis by amphotericin B. These include unique host-based risk factors for mucormycosis, the fungus' resistance to innate host defenses and distinctive features of its immunopathogenesis, such as extensive angioinvasion, increased virulence and use of chelators by the fungus as siderophores.…”